Prevention of SARS-CoV-2 in Hospital Workers s Exposed to the Virus (PREP-COVID)

Randomized Multicenter Study Evaluating the Efficacy of Azithromycin and Hydroxychloroquine in the Prevention of SARS-CoV-2 Infection in the Hospital Population Exposed to Virus

The Investigators propose to set up a preventive trial of infection in hospital workers at risk of coronavirus infection by comparing the rate of SARS-Cov-2 infection in a population of negative SARS-Cov-2 hospital workers receiving preventively azithromycin, hydroxychloroquine or a Placebo

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Drug: hydroxychloroquine; Drug: hydroxychloroquine placebo; Drug: azithromycin

Detailed Description

Randomized clinical trial with 3 arms : hydroxychloroquine group, 300 subjects/azithromycin group, 300 subjects/ placebo of hydroxychloroquine group, 300 subjects. Hospital workers workers will be invited to participate in the study in each hospital and they will be included after giving their consent, assessment of their eligibility criteria, endonasal PCR and serolology at baseline. They will be randomized in one of the 3 arms, receive their treatment and will be followed by physical visit (at Day 2, Day 5, Day 15, Day 28) and by phone (at Day) 40 days with clinical data collection (tolerance and clinical signs of infection). At the end of treatment, another serology will be collected.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bobigny, France, 93000
    • Hopial Avicenne
  • Le Kremlin-Bicêtre, France, 92100
    • Hôpital GHU Paris Saclay
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Paris, France, 75012
    • Hopital Saint Antoine
  • Paris, France, 75014
    • Hôpital Cochin
  • Paris, France, 75013
    • Hopital Broca
  • Paris, France, 75013
    • Hôpital La Pitié-Salpêtrière
  • Paris, France, 75015
    • Hôpital Necker

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Hospital workers working at AP-HP hospitals over the age of 18

• Hospital workers who have signed consent
• No signs of COVID-19 infection
• Women who are likely to procreate should have a negative pregnancy test on inclusion day. In addition, they should use at least one effective contraceptive method before starting treatment, during treatment and up to 8 months after the last drug tested during the trial. Sexually active men should also have effective contraception during treatment and for at least 8 months after the last drug tested during the trial.
• Affiliated or beneficiary of Social Security

Exclusion Criteria:

• History of SARS-CoV-2 infection confirmed by PCR or serology is available at inclusion
• A history of clinical episode suspecting a PCR-confirmed or unconfirmed COVID-19 infection.
• Pregnancy and breastfeeding
• Allergy or contraindications to one of the 2 drugs in the study
• Known retinopathy
• Long congenital QT syndrome (or known in the family)
• QTc or 450 ms in men, or 460 ms in women, if Fc 55/mn (except in case of intense sport practice), if ESV on baseline ECG, if QRS - or 120 ms, if AC/FA, if the PR or BAV lengthening
• History of severe ischemic heart disease or unbalanced heart failure.
• Clinically significant bradycardia known
• Known kidney or liver failure
• Known G6PD deficit
• Subject who received antiviral treatment in the 14 days prior to inclusion
• Subject who had treatment with azithromycin or hydroxychloroquine, in the 14 days prior to inclusion
• Hypokaliemia (<= 3.5 mmol/L), Increase in creatinine (>=120 micromol/Ll, Increase in transaminases at baseline (>=2N)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm Title : hydroxychloroquine	Drug: hydroxychloroquine; 200 mg BID per day
Placebo Comparator: Placebo of hydroxychloroquine	Drug: hydroxychloroquine placebo; 200 mg BID per day
Active Comparator: azythromycin	Drug: azithromycin; 250 mg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of hydroxychloroquine and azithromycin on the prevention of SARS-CoV-2 contamination in hospital workers exposed to 40 days of treatment.	The number of hospital workers with a positive serology or a positive PCR within 40 days of follow-up.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reducing clinical episodes due to suspected SARS-2 CoV infection confirmed by PCR	Clinical signs suggesting SARS-2 CoV infection confirmed by positive endonasal PCR	40 days
Reducing seroconversion for SARS-CoV-2 without any clinical sign	number of seroconversion by serology between Day 0 and Day 40.	3 months
Evaluation of drug tolerance in the study	number of cardiological severe adverse events assessed (ECG abnormalities : widening QT, ventricular arythmia, and cardiac arrests), other serious adverse events including hospitalizations, and deaths	40 days
Evaluation on work stopping of hospital workers	Number of work stoppages over the period	40 days
Observance of treatment measured by plasmatic concentrations of hydroxychloroquine or azythromycine	Plasmatic concentrations of treatments	40 days
Incidence of cardiologic events	number of cardiac events, especialy ECG abnormalities (widening QT) due to treatments	40 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Jean Ma Treluyer, MD PhD, Assitance publique - Hôpitaux de Paris.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2020
• Primary Completion (Actual): June 18, 2020
• Study Completion (Actual): June 18, 2020

Study Registration Dates

• First Submitted: March 27, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: July 31, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; caregivers; hydroxychloroquine; azithromycin
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: APHP200386; 2020-001273-73 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No